Search

Purpose: The conventional method to reconstruct the bone level for orbital defects, which is based on mirroring and manual adaptation, is time-consuming and the accuracy highly depends on the expertise of the clinical engineer. The aim of this study is to propose and evaluate an automated reconstruction method utilizing a Gaussian process morphable model (GPMM)., Methods: Sixty-five Computed Tomography (CT) scans of healthy midfaces were used to create a GPMM that can model shape variations of the orbital region. Parameter optimization was performed by evaluating several quantitative metrics inspired on the shape modeling literature, e.g. generalization and specificity. The reconstruction error was estimated by reconstructing artificial defects created in orbits from fifteen CT scans that were not included in the GPMM. The developed algorithms utilize the existing framework of Gaussian process morphable models, as implemented in the Scalismo software., Results: By evaluating the proposed quality metrics, adequate parameters are chosen for non-rigid registration and reconstruction. The resulting median reconstruction error using the GPMM was lower (0.35 ± 0.16 mm) compared to the mirroring method (0.52 ± 0.18 mm). In addition, the GPMM-based reconstruction is automated and can be applied to large bilateral defects with a median reconstruction error of 0.39 ± 0.11 mm., Conclusion: The GPMM-based reconstruction proves to be less time-consuming and more accurate than reconstruction by mirroring. Further validation through clinical studies on patients with orbital defects is warranted. Nevertheless, the results underscore the potential of GPMM-based reconstruction as a promising alternative for designing patient-specific implants., (© 2024. CARS.)

Objective: Early detection significantly improves the prognosis of oral cancer patients, contingent upon the knowledge of dental professionals. This study aimed to assess and compare the knowledge, practices and perceptions regarding oral cancer among dental professionals in Belgium., Materials and Methods: A cross-sectional survey was distributed via Qualtrics to general dentists, dental specialists, dental hygienists, and oral and maxillofacial surgeons. The self-administered questionnaire comprised three sections: demographics (4 questions), knowledge (9 questions) and clinical practices (19 questions) related to oral cancer detection and treatment. Descriptive statistics were employed for data analysis, with Chi-square tests assessing responses by specialization, gender, years of experience and number of oral cancer patients treated., Results: A total of 262 questionnaires were completed, with the majority of respondents being general dentists (61%) followed by dental specialists (25%), oral hygienists (8%) and oral and maxillofacial surgeons (6%). 70% of the respondents reported treating fewer than four oral cancer patients throughout their careers. 5 out of the 9 knowledge questions achieved over 50% correct responses, with an average correct answer rate of 54%. Oral and maxillofacial surgeons and dental professionals who have treated more than four oral cancer patients, demonstrated significantly higher scores on multiple knowledge questions. Responses to clinically oriented questions showed less diversity across professions, and generally aligning with guidelines from professional oncological societies., Conclusion: This survey highlights the need for enhanced education on oral cancer among Belgian dental professionals. Knowledge levels were notably higher among more experienced respondents. The development and implementation of comprehensive guidelines tailored to dentists and oral hygienists for oral cancer prevention and patient care are warranted to optimize clinical practice standards., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest regarding this analysis., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Magnesium is the most promising absorbable metallic implant material for bone regeneration and alloy WE43 is already FDA approved for cardiovascular applications. This study investigates the cyto- and biocompatibility of novel additively manufactured (AM) porous WE43 scaffolds as well as their osteogenic potential and degradation characteristics in an orthotopic canine bone defect model. The cytocompatibility was demonstrated using modified ISO 10993-conform extract-based indirect and direct assays, respectively. Additionally, degradation rates of WE43 scaffolds were quantified in vitro prior to absorption tests in vivo. Complete blood cell counts, blood biomarker analyses, blood trace element analyses as well as multi-organ histopathology demonstrated excellent biocompatibility of porous y WE43 scaffolds for bone defect repair. Micro-CT analyses further showed a relatively higher absorption rate during the initial four weeks upon implantation (i.e., 36 % ± 19 %) than between four and 12 weeks (41 % ± 14 %), respectively. Of note, the porous WE43 implants were surrounded by newly formed bony tissue as early as four weeks after implantation when unmineralized trabecular ingrowth was detected. After 12 weeks, a substantial amount of mineralized bone was detected inside and around the gradually disappearing implants. This first study on AM porous WE43 implants in canine bone defects demonstrates the potential of this alloy for in vivo applications in humans. Our data further underscore the need to control initial bulk absorption kinetics through surface modifications., Competing Interests: Declaration of competing interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Cancer patients often receive a combination of antibodies targeting programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen-4 (CTLA4). We conducted a window-of-opportunity study in head and neck squamous cell carcinoma (HNSCC) to examine the contribution of anti-CTLA4 to anti-PD-L1 therapy. Single-cell profiling of on- versus pre-treatment biopsies identified T cell expansion as an early response marker. In tumors, anti-PD-L1 triggered the expansion of mostly CD8 + T cells, whereas combination therapy expanded both CD4 + and CD8 + T cells. Such CD4 + T cells exhibited an activated T helper 1 (Th1) phenotype. CD4 + and CD8 + T cells co-localized with and were surrounded by dendritic cells expressing T cell homing factors or antibody-producing plasma cells. T cell receptor tracing suggests that anti-CTLA4, but not anti-PD-L1, triggers the trafficking of CD4 + naive/central-memory T cells from tumor-draining lymph nodes (tdLNs), via blood, to the tumor wherein T cells acquire a Th1 phenotype. Thus, CD4 + T cell activation and recruitment from tdLNs are hallmarks of early response to anti-PD-L1 plus anti-CTLA4 in HNSCC., Competing Interests: Declaration of interests P.M.C. reports the mentioned grant and non-financial support from AstraZeneca during the study; personal fees and non-financial support from AbbVie, Bayer, Bristol-Myers Squibb, Merck, LEO Pharma, and Vifor Pharma; personal fees from Daiichii Sankyo, and Rakuten; and non-financial support from Teva, Novartis, Amgen, and Roche outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Immune checkpoint inhibitors (ICI) have introduced a new era in the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Optimal duration for ICI therapy is still unclear and the long-term outcomes and toxicity in patients responding to these therapies warrant further exploration. This study attempts to identify the clinical and biological determinants of a durable response and evaluate outcomes following ICI treatment discontinuation., Materials and Methods: A retrospective review of 181 patients treated with ICI for R/M HNSCC was conducted. Long-term responders were defined as patients who sustained disease control at least two years after initiating ICI therapy. We compared clinical and biological characteristics associated with these long-term responders against the broader treatment population., Results: 10 % of R/M HNSCC patients treated with ICIs demonstrated a durable long-term response. Only three relapses (16 %) occurred after discontinuing ICI treatment in this subset, with a median follow-up of 52 months. Upon retreatment with ICI, two attained a documented response. Extended ICI response was observed even with < 2 years of treatment. 74 % of long-term responders experienced immune-related adverse events (irAEs), 37 % of which severe irAEs. Hypothyroidism was the most frequently reported irAEs. The predictive potential of systemic inflammation indices for clinical response appears to be limited., Conclusions: ICI present an optimistic avenue for HNSCC patients, offering substantial long-term responses. The study suggests that a two-year treatment could be optimal and irAEs, although common, are typically mild., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder in which many patients also have neurobehavioral problems. Corticosteroids, the primary pharmacological treatment for DMD, have been shown to affect brain morphology in other conditions, but data in DMD are lacking. This study aimed to investigate the impact of two corticosteroid regimens on brain volumetrics in DMD using magnetic resonance imaging (MRI)., Methods: In a cross-sectional, two-center study, T1-weighted MRI scans were obtained from three age-matched groups (9-18 years): DMD patients treated daily with deflazacort (DMDd, n = 20, scan site: Leuven), DMD patients treated intermittently with prednisone (DMDi, n = 20, scan site: Leiden), and healthy controls (n = 40, both scan sites). FSL was used to perform voxel-based morphometry analyses and to calculate intracranial, total brain, gray matter, white matter, and cerebrospinal fluid volumes. A MANCOVA was employed to compare global volumetrics between groups, with site as covariate., Results: Both patient groups displayed regional differences in gray matter volumes compared to the control group. The DMDd group showed a wider extent of brain regions affected and a greater difference overall. This was substantiated by the global volume quantification: the DMDd group, but not the DMDi group, showed significant differences in gray matter, white matter, and cerebrospinal fluid volumes compared to the control group, after correction for intracranial volume., Interpretation: Volumetric differences in the brain are considered part of the DMD phenotype. This study suggests an additional impact of corticosteroid treatment showing a contrast between pronounced alterations seen in patients receiving daily corticosteroid treatment and more subtle differences in those treated intermittently., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Mandibular reconstruction with free fibular flaps is frequently used to restore segmental defects. The osteosythesis, including locking and non-locking plate/screw systems, is essential to the mandibular reconstruction. Compared with the non-locking system that requires good adaption between plate and bone, the locking system appears to present a better performance by locking the plate to fixation screws. However, it also brings about limitations on screw options, a higher risk of screw failure, and difficulties in screw placement. Furthermore, its superiority is undermined by the advancing of patient-specific implant design and additive manufacturing. A customized plate can be designed and fabricated to accurately match the mandibular contour for patient-specific mandibular reconstruction. Consequently, the non-locking system seems more practicable with such personalized plates, and its biomechanical feasibility ought to be estimated. Finite element analyses of mandibular reconstruction assemblies were conducted for four most common segmental mandibular reconstructions regarding locking and non-locking systems under incisal biting and right molars clenching, during which the influencing factor of muscles' capacity was introduced to simulate the practical loadings after mandibular resection and reconstruction surgeries. Much higher, somewhat lower, and similar maximum von Mises stresses are separately manifested by the patient-specific mandibular reconstruction plate (PSMRP), fixation screws, and reconstructed mandible with the non-locking system than those with the locking system. Equivalent maximum displacements are identified between PSMRPs, fixation screws, and reconstructed mandibles with the non-locking and locking system in all four reconstruction types during two masticatory tasks. Parallel maximum and minimum principal strain distributions are shared by the reconstructed mandibles with the non-locking and locking system in four mandibular reconstructions during both occlusions. Conclusively, it is feasible to use the non-locking system in case of patient-specific mandibular reconstruction with fibular free flaps based on the adequate safety, comparable stability, and analogous mechanobiology it presents compared with the locking system in a more manufacturable and economical way., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Response rates of immune checkpoint inhibitor (ICI) therapy for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are low., Patients and Methods: This retrospective multicentre cohort study evaluates the predictive and prognostic value of weight loss and changes in body composition prior and during therapy. Patient, tumor, and treatment characteristics of 98 patients were retrieved, including neutrophil and platelet-lymphocyte-ratio (NLR and PLR). Programmed death-ligand 1 (PD-L1) expression was determined on residual material. Cachexia was defined according to Fearon et al. (2011). Skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were evaluated on computed tomography scans at the third lumbar vertebrae level. Univariable and multivariable regression analyses were performed for 6 months progression free survival (PFS6m) and overall survival (OS)., Results: Significant early weight loss (>2%) during the first 6 weeks of therapy was shown in 34 patients (35%). This patient subgroup had a significantly higher NLR and PLR at baseline. NLR and PLR were inversely correlated with SM and VAT index. Independent predictors of PFS6m were lower World Health Organization performance status (HR 0.16 [0.04-0.54] p = 0.003), higher baseline SAT index (HR 1.045 [1.02-1.08] p = 0.003), and weight loss <2% (HR 0.85 [0.74-0.98] p = 0.03). Baseline cachexia in combination with >2% early weight loss remained a predictor of OS, independent of PD-L1 expression (HR 2.09 [1.11-3.92] p = 0.02, HR 2.18 [1.13-4.21] p = 0.02)., Conclusion: We conclude that the combination of cachexia at baseline and weight loss during ICI therapy is associated with worse OS in R/M HNSCC patients, independent of PD-L1 expression., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: The aim of this study is to investigate the long-term effects on jaw and femur bone induced by oncologic doses of zoledronic acid in a young rat model., Material and Methods: Six 12-week-old male Wistar rats received zoledronic acid (0.6 mg/kg) and six control rats received saline solution in the same volume. Compounds were administered intraperitoneally in five doses every 28 days. Euthanasia was performed 150 days after therapy onset. After animal sacrifice, their mandibles and femurs were scanned ex vivo using a high-resolution (14 μm) micro-computed tomography. Morphometric bone parameters were calculated using CT-Analyzer (Bruker, Belgium) between the first and second mandibular molars and in the distal femur metaphysis and epiphysis., Results: The treatment group as compared to the controls showed a significantly (p < .05) increased bone quantity (↑BV/TV, ↓Po[Tot], ↑Tb.Th), bone density (↑TMD, ↑BMD), and osteosclerosis of the trabecular bone (↓Tb.Sp, ↓Conn.Dn, ↓Tb.Pf, ↓SMI) in all anatomical sites. Bone remodeling suppression due to zoledronic acid treatment was more pronounced (p < .05) in the femoral metaphysis relative to the mandible and epiphysis. The exploratory linear discriminant analysis showed that for the mandible, it was mainly the bone quantity-related morphometric indices (BV/TV and Tb.Th), while for the femoral epiphysis and metaphysis, it was bone structure-related (Tb.Pf and Tb.N), which are of primary importance to study the treatment effect., Conclusion: High doses of bisphosphonates can differently affect the bone quantity, density, and structure in long bones and jawbones. In the metaphysis, bone changes were primarily concentrated in the region of the growth plate. Future studies may consider the use of bone morphometric indices to evaluate the effect of bisphosphonates., (© 2022 The Authors. Clinical and Experimental Dental Research published by John Wiley & Sons Ltd.)

Background and Objective: Owing to the unexpected in vivo fracture failure of the original design, structural optimized patient-specific mandibular reconstruction plates (PSMRPs) were created to boost the biomechanical performance of bridging segmental bony defect in the mandibular reconstruction after tumor resection. This work aimed to validate the biomechanical benefit of the structural optimized PSMRPs relative to the original design and compare the biomechanical performance between PSMRP1 with generic contour customization and PSMRP2 with a tangent arc upper margin in mandibular angle region., Methods: Finite Element Analysis (FEA) was used to evaluate the biomechanical behavior of mandibular reconstruction assemblies (MRAs) concerning these two structural optimized PSMRPs by simulating momentary left group clenching and incisal clenching tasks. Bonded contact was set between mandibular bone and fixation screws and between PSMRP and fixation screws in the MRA, while the frictionless connection was allocated between mandibular bone and PSMRP. The loads were applied on four principal muscles, including masseter, temporalis, lateral and medial pterygoid, whose magnitudes along the three orthogonal directions. The mandibular condyles were retrained in all three directions, and either the left molars or incisors area were restrained from moving vertically., Results: The peak von Mises stresses of structural optimized PSMRPs (264 MPa, 296 MPa) were way lower than that of the initial PSMRP design (393 MPa), with 33 and 25% reduction during left group clenching. The peak magnitude of von Mises stress, minimum principal stress, and maximum principal strain of PSMRP1 (264 MPa, 254 MPa; -297 MPa, -285 MPa; 0.0020, 0.0020) was lower than that of PSMRP2 (296 MPa, 286 MPa; -319 MPa, -306 MPa; 0.0022, 0.0020), while the peak maximum principal stress of PSMRP1 (275 MPa, 257 MPa) was higher than that of PSMRP2 (254 MPa, 235 MPa) during both left group clenching and incisal clenching tasks., Conclusions: The structural optimized PSMRPs reveal their biomechanical advantage compared with the original design. The PSMRP1 presents better biomechanical performance to the patient-specific mandibular reconstruction than PSMRP2 as a result of its superior safety, preferable flexibility, and comparable stability. The PSMRP2 provides biomechanical benefit in reducing the maximum tension than PSMRP1, indicated by lower peak maximum principal stress, through tangent arc upper margin in mandibular angle region., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study used a novel 3D analysis to longitudinally evaluate orthodontic tooth movement (OTM) and bone morphometry. Twelve-week-old male Wistar rats were subjected to OTM by applying a constant orthodontic force (OF) of 25cN between one of the upper first molars and a mini-screw. In vivo micro-CTs were taken before and after 10, 17, 24 and 31 days of force application, and superimposed by a novel and rigid voxel-based registration method. Then the tooth and alveolar bone segment at different time points became comparable in the same coordinate system, which facilitated the analysis of their dynamic changes in 3D. By comparison between time points and between OF and no OF sides, this study showed that the OTM rate was not constant through time, but conformed to a 'V' shape changing pattern. Besides, OF induced displacement of both loaded and unloaded teeth, and the latter mirrored the former in a delayed manner. In addition, bone morphometric changes synchronized with OTM rate changes, implying that a higher OTM rate was concomitant with more alveolar bone loss. The pressure and tension areas might not be in two opposite sides, but actually adjacent and connected. These findings might provide instructive evidence for both clinical, translational and basic research in orthodontics., (© 2022. The Author(s).)

Functional magnetic resonance imaging studies have reported a diminished response in the brain's reward circuits to contingent cues predicting future monetary gain in adolescents with attention-deficit/hyperactivity disorder (ADHD). The situation with regard to monetary loss is less clear, despite recognition that both positive and negative consequences impact ADHD behaviour. Here, we employ a new Escape Monetary Loss Incentive task in an MRI scanner, which allows the differentiation of contingency and valence effects during loss avoidance, to examine ADHD-related alterations in monetary loss processing. There was no evidence of atypical processing of contingent or non-contingent monetary loss cues in ADHD - either in terms of ratings of emotional and motivational significance or brain responses. This suggests that the ability to process contingencies between performance and negative outcomes is intact in ADHD and that individuals with ADHD are no more (or less) sensitive to negative outcomes than controls. This latter finding stands in stark contrast to recent evidence from a similar task of atypical emotion network recruitment (e.g. amygdala) in ADHD individuals to cues predicting another negative event, the imposition of delay, suggesting marked specificity in the way they respond to negative events., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Comorbidities influence treatment outcome of oral squamous cell carcinoma (OSCC). This study compared the predictive performance of six comorbidity scales for overall survival after surgery for OSCC., Methods: We retrospectively analyzed OSCC patients, surgically treated at an academic center in Belgium between January 01, 2000 and January 01, 2020. Validity of the scales was evaluated using the area under the curve (AUC) of receiver operating characteristic curves., Results: Three hundred and twenty three patients were included. Elixhauser Comorbidity Index (AUC = 0.74, 95% CI: 0.55-0.92; AUC = 0.73, 95% CI: 0.55-0.80), modified Elixhauser Comorbidity Index (AUC = 0.72, 95% CI: 0.54-0.91; AUC = 0.69, 95% CI: 0.51-0.77), and Combined Comorbidity Index (AUC = 0.76, 95% CI: 0.58-0.84; AUC = 0.76, 95% CI: 0.59-0.84) were meaningful predictors for 2 and 5-year survival, respectively., Conclusion: Selected comorbidity scales were capable of predicting overall survival for OSCC patients 2 and 5 years after primary surgery., (© 2022 Wiley Periodicals LLC.)

Objective: (1) To test the accuracy of split-mouth models in rats for the study of orthodontic tooth movement (OTM) and (2) to propose an improved 3D model for quantification of OTM in rats., Methods: Eleven Wistar rats were split into group 1 (dental anchorage) and group 2 (skeletal anchorage). In both groups, no orthodontic force (OF) was applied on the contralateral hemi-maxilla. In vivo micro-CT images were taken before (T0) and 31 days (T1) after OF. OTM was compared between time-points and experimental sides using conventional 2D analysis and a novel 3D model., Results: Using incisors as anchorage leads to their distal displacement in both OF and no OF sides. In the OF side, movement of M1 is underestimated by incisor displacement. Mesial displacement of M1 was found in the no OF side of all groups 31 days after the application of OF., Conclusions: The new 3D model yielded higher sensitivity for tooth displacement in planes other than sagittal and incisor displacement was reduced by using skeletal anchorage., Clinical Significance: Studies following split-mouth designs in orthodontic research in rats might be systematically underestimating the effects of techniques and/or medication on OTM, since there is tooth displacement on the control side. 3D quantification of OTM with skeletal anchorage is more sensitive and avoids displacement of the dental units used as anchorage., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: The aim of the study was to assess the 5-year cumulative survival rate of implant-based dental rehabilitation following maxillofacial reconstruction with a vascularized bone flap and to investigate the potential risk factors which might influence the survival rate., Materials and Methods: A retrospective cohort study was designed. Inclusion criteria involved 18 years old or above patients with the availability of clinical and radiological data and a minimum follow-up 1 year following implant placement. The cumulative survival rate was analyzed by Kaplan-Meier curves and the influential risk factors were assessed using univariate log-rank tests and multivariable Cox-regression analysis., Results: 151 implants were assessed in 40 patients with a mean age of 56.43 ± 15.28 years at the time of implantation. The mean number of implants placed per patient was 3.8 ± 1.3 with a follow-up period of 50.0 ± 32.0 months. The cumulative survival at 1-, 2- and 5-years was 96%, 87%, and 81%. Patients with systemic diseases (HR = 3.75, 95% CI 1.65-8.52; p = 0.002), irradiated flap (HR = 2.27, 95% CI 1.00-5.17; p = 0.05) and poor oral hygiene (HR = 11.67; 95% CI 4.56-29.88; p < 0.0001) were at a significantly higher risk of implant failure., Conclusion: The cumulative implant survival rate was highest at 1st year followed by 2nd and 5th year, indicating that the risk of implant failure increased over time. Risk indicators that seem to be detrimental to long-term survival include poor oral hygiene, irradiated flap and systemic diseases., (© 2022. The Author(s).)

Objective: The treatment approach of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) has long been similar for all patients. Any difference in treatment strategy was only based on existing comorbidities and on preferences of the patient and the treating oncologist. The recent advance obtained with immune therapy and more specifically immune checkpoint blockade (ICB) has been a true game changer. Today, patients and physicians have a choice to omit chemotherapy. In a small subset of patients, ICB induces a very durable disease control. The subgroup of patients in which ICB without chemotherapy would be the preferential approach is still ill-defined. Yet, this evolution marks a major step towards a more personalized medicine in R/M HNSCC., Materials and Methods: In this paper, we present a retrospective cohort study of a patient population that was treated with ICB in a single center and we analyze potential factors that are associated with outcome and may help to select patients for treatment with ICB., Results: 137 consecutively treated patients were identified. Male gender and metastatic disease appeared to be associated with improved overall survival (OS). There was no correlation observed with age, number of previous treatment lines or immune target., Conclusion: Along with PD-L1 status defined by Combined Positive Score (CPS), clinical parameters such as site of recurrence and gender may help to define the optimal treatment strategy in R/M HNSCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bila, Van Dessel, Smeets, Vander Poorten, Nuyts, Meulemans and Clement.)

Patient-specific mandibular reconstruction plate (PSMRP), as one of the patient-specific implants (PSIs), offers a host of benefits to mandibular reconstruction. Due to the limitation of fabricating screw hole threads in the PSMRP, 3D printed PSMRP is applied to the non-locking system directly in the mandibular reconstruction with bone graft regardless of the locking system. Since the conventional manual-bending reconstruction plate (CMBRP) provides better fixation in the locking system, it needs to be validated whether the locking PSMRP performs better than the non-locking PSMRP in the patient-specific mandibular reconstruction. Thereupon, the purpose of this study was to compare the biomechanical behavior between the locking and non-locking PSMRP. Finite element analysis (FEA) was used to conduct the biomechanical comparison between the locking PSMRP and non-locking PSMRP by simulating the momentary incisal clenching through static structural analysis. Mandible was reconstructed through the virtual surgical planning, and subsequently a 3D model of mandibular reconstruction assembly, including reconstructed mandible, PSMRP, and fixation screws, was generated and meshed for the following FEA simulations. In the form of equivalent von Mises stress, equivalent elastic strain, and total deformation, the locking PSMRP demonstrated its higher strengths of preferable safety, desirable flexibility, and anticipated stability compared with the non-locking PSMRP, indicated by much lower maximum stress, lower maximum strain and equivalent displacement. Locking PSMRP/screw system provides a better fixation effect to the patient-specific mandibular reconstruction than the non-locking one as a result of its productive fixation nature. FEA plays a paramount role in pre-validating the design of PSMRP through the biomechanical behavior evaluation in static structural analysis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: A combination of short titanium plates fabricated using additive manufacturing (AM) provides multiple advantages for complete mandible reconstruction, such as the minimisation of inherent implant deformation formed during AM and the resulting clinical impact, as well as greater flexibility for surgical operation. However, the biomechanical feasibility of this strategy is still unclear, and therefore needs to be explored., Method: Three different combinations of short mandible reconstruction plates (MRPs) were customised considering implant deformation during the AM process. The resulting biomechanical performance was analysed by finite element analysis (FEA) and compared to a conventional single long MRP., Results: The combination of a long plate and a short plate (Design 3 [LL61 mm/RL166 mm]) shows superior biomechanical properties to the conventional single long plate (Design 1 [TL246 mm]) and reveals the most reliable fixation stability among the three designs with short plates. Compared to conventional Design 1, Design 3 provides higher plate safety (maximum tensile stress on plates reduced by 6.3%), lower system fixation instability (relative total displacement reduced by 41.4%), and good bone segment stability (bone segment dislocation below 42.1 μm) under masticatory activities., Conclusions: Preclinical evidence supports the biomechanical feasibility of using short MRPs for complete mandible reconstruction. Furthermore, the results could also provide valuable information when treating other large-sized bone defects using short customised implants, expanding the potential of AM for use in implant applications., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Abstract: This study aims to evaluate the use of customized surgical plates in patients with mandibular defects concerning postoperative aesthetics and functional outcomes during the 2-year follow-up. Preoperative virtual surgical plans and patient-specific three-dimensional printed plates were tailored for consecutive patients. Preoperative preparation, surgical produces, postoperative aesthetics, and functional outcomes were described in detail. The average follow-up period was over 2 years. In the presented clinical cases, aesthetic and functional outcomes were reported to be satisfactory., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Objective: To investigate the adherence to initially planned maxillofacial reconstructions using computer-assisted surgery (CAS) and to identify the influential factors affecting its compliance for maxillofacial reconstruction., Patients and Methods: A retrospective analysis of 136 computer-assisted maxillofacial reconstructive surgeries was conducted from January 2014 to June 2020. The categorical parameters involved age, gender, disease etiology, disease site, defect size, bone flap segments, and flap type. Apart from descriptive data reporting, categorical data were related by applying the Fisher-exact test, and a p-value below 5% was considered statistically significant (P < 0.05)., Results: The main reasons for partial or non-adherence included unfitness, patient health condition, and other subjective reasons. Out of the total patient population, 118 patients who underwent mandibular reconstruction showed higher CAS compliance (83.9%) compared to the 18 midface reconstruction (72.2%) without any statistically significant difference (p = 0.361). Based on the size of the defect, a significantly higher CAS compliance (p = 0.031) was observed with a minor defect (80.6%) compared to the large-sized ones (74.1%). The bone flaps with two or more segments were significantly (p = 0.003) prone to observe a partial (15.4%) or complete (12.8%) discard of the planned CAS compared to the bone flaps with less than two segments. The malignant tumors showed the lowest CAS compliance when compared to other disorders without any significant difference (p = 0.1)., Conclusion: The maxillofacial reconstructive surgical procedures offered optimal compliance to the initially planned CAS. However, large-sized defects and multiple bone flap segments demonstrated a higher risk of partial or complete abandonment of the CAS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ma, Shujaat, Van Dessel, Sun, Bila, Vranckx, Politis and Jacobs.)

Aim: To evaluate dimensional changes in the alveolar ridge and bone structure after tooth extraction when L-PRF or A-PRF+ was used in comparison to unassisted socket healing., Materials and Methods: Twenty patients in need of at least three tooth extractions in the aesthetic zone were included. L-PRF, A-PRF+ or control was randomly assigned, leaving one empty socket/edentulous site between conditions. CBCT scans were obtained immediately after tooth extraction and after 3 months of healing. Horizontal and vertical dimensional changes of the ridge and socket fill were calculated. Histological and micro-CT analysis of bone biopsies were used to evaluate post-surgical bone structural healing., Results: Mean horizontal and vertical changes at 1-mm below the crest (buccal and palatal side) were similar for the three sites (p > 0.05). For the socket fill, L-PRF (85.2%) and A-PRF+ (83.8%) showed superior values than the control (67.9%). The histological and radiological analysis reported more newly formed bone for the PRF groups, without any significant differences between both., Conclusions: PRF matrices failed to reduce the dimensional changes after multiple tooth extractions in the premaxilla. After 3-month healing, both PRF matrices showed radiographically a significant superiority for the socket fill. Histologically, they seemed to accelerate new bone formation., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Negative reinforcement processes allow individuals to avoid negative and/or harmful outcomes. They depend on the brain's ability to differentiate; (i) contingency from non-contingency, separately from (ii) judgements about positive and negative valence. Thirty-three males (8-18 years) performed a cued reaction-time task during fMRI scanning to differentiate the brain's responses to contingency and valence during loss avoidance. In two conditions, cues indicated no -contingency between participants' responses and monetary loss - (1) CERTAIN LOSS (negative valence) of €0.20, €1 or €5 or (2) CERTAIN LOSS AVOIDANCE (positive valence). In a third condition, cues indicated a contingency between short reaction times and avoidance of monetary loss. As expected participants had shorter reaction times in this latter condition where CONDITIONAL LOSS AVOIDANCE cues activated salience and motor-response-preparation brain networks - independent of the relative valence of the contrast (CERTAIN LOSS or CERTAIN LOSS AVOIDANCE). Effects of valence were seen toward the session's end where CERTAIN LOSS AVOIDANCE cues activated ventral striatum, medial-orbitofrontal cortex and medial-temporal areas more than CERTAIN LOSS. CONDITIONAL LOSS AVOIDANCE trials with feedback indicating "success" activated ventral striatum more than "failure feedback". The findings support the hypothesis that brain networks controlling contingency and valence processes during negative reinforcement are dissociable., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Bone-to-implant contact ratio (BIC%) plays a critical role in secondary stability of osseointegrated dental implants. The aim of this study was to identify the correlation of 2D/3D micro-CT images with histology as a gold standard for evaluating BIC% and to investigate the influence of the platelet-rich plasma (PRP) and platelet-poor plasma (PPP) on 3D BIC% following delayed implant placement with delayed loading (DIP+DL)., Methods: Nine beagle dogs were recruited. Following bilateral extraction of mandibular 3rd premolar, 4th premolar, and 1st molar, 54 screw-type titanium implants were inserted and randomly divided into one control and two test groups based on a split-mouth design. The control group involved DIP+DL (n = 18) and both test groups included DIP+DL with local application of PRP (n = 18) and PPP (n = 18). A BIC analysis was performed utilizing 2D histomorphometry and 2D/3D micro-CT. Following identification of correlation between histology and 2D/3D micro-CT images, a 3D micro-CT assessment of the 3D BIC% at three follow-up time-points (1, 3, and 6 months) was carried out for observing the influence of PRP and PPP on BIC., Results: The 2D micro-CT BIC% values revealed a strong positive correlation with histology (r = 0.98, p < 0.001) and a moderate correlation existed with 3D micro-CT (r = 0. 67, p = 0.005). BIC levels at 1 month and combined influence of PPP and PRP irrespective of time-points revealed significantly higher 3D BIC% compared to the control. However, a reduction in 3D BIC% was observed at the 3rd and 6th month. No significant difference was observed between both PRP and PPP., Conclusions: Both 2D and 3D micro-CT demonstrated a potential to be utilized as a complimentary method for assessing BIC compared to the histological gold standard. Overall, both PRP and PPP significantly facilitated bone healing and osseointegration with a higher 3D BIC at follow-up. However, their influence was reduced as the observation period was increased.

Introduction: To date, there is a lack of evidence related to the long-term evaluation of recipient-site functional outcomes following mandibular reconstruction with vascularized bone grafts. Therefore, the aim of this systematic review and meta-analysis was to evaluate the long-term recipient-site functional outcomes in oral oncology patients who require mandibular reconstruction with either vascularized fibular flap (VFF) or vascularized iliac flap (VIF)., Methods: An extensive electronic search was conducted in PubMed, Web of Science, Cochrane, and Embase databases for identifying articles published until April 2020. All papers were dual screened for eligibility in accordance with the Preferred Reporting of Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology guidelines. The risk of bias was assessed using the MINORS tool. A meta-analysis of functional outcome parameters was performed to estimate single incidence rates., Results: A total of 257 patients with a mean follow-up period of 38.6 ± 19.5 months were included in this meta-analysis, where 174 patients underwent VFF reconstruction and 83 patients involved reconstruction with VIF. The functional outcomes in patients reconstructed with VIF showed improved scoring for mastication, deglutition, diet, and speech. Speech showed highest score among all functional parameters, whereas, mastication was the most poorly recovered parameter in relation to reconstruction with both flaps. No significant difference in functional outcomes was observed between both flaps., Conclusion: Current evidence seems to indicate that VIF offers improved long-term recipient-site functional outcomes. Yet, considering a high level of data heterogeneity in published studies, future long-term standardized comparative studies should be conducted., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Academic impairment in individuals with attention-deficit/hyperactivity disorder (ADHD) is in part due to reduced motivation for academic tasks, which is likely to vary as a function of task characteristics. The current study employed a new questionnaire-the Child and Adolescent Motivational Profile (CHAMP)-to examine; (1) which task characteristic participants with ADHD perceive as most motivating relative to typically developing peers (TDP) and (2) whether these differences mediate academic functioning. 34 participants with ADHD and 435 TDP (8-16 years) completed the CHAMP. Academic achievement (grade point average) and self-reported positive/negative classroom experiences were recorded. No task characteristics were rated higher in terms of their motivational salience in the ADHD group than in the control sample. Marked/graded, Socially evaluated, Collaborative, Requiring focus and Cognitively challenging task characteristics were rated significantly lower by the ADHD group than controls. The lower rating of Socially evaluated was explained by comorbid ODD symptoms. Cognitively challenging was rated as particularly unmotivating by individuals with ADHD. ADHD was associated with a decreased GPA and a more negative classroom experience. The associations between ADHD and GPA/negative classroom experience were both partially mediated by scores on the Cognitively Challenging scale. For children and adolescents with ADHD tasks that are cognitively challenging were not particularly motivating. To increase task motivation, and improve academic performance of individuals with ADHD, it may be important to include rewarded task elements as they are appraised as particularly motivating by these individuals and this appraisal was similar to that of TDP.

Objectives: Recent magnetic resonance imaging (MRI) studies implicate structural alterations of amygdala, a brain region responsible for processing and experiencing negative emotions, in adolescents with attention-deficit/hyperactivity disorder (ADHD). Here we examined ADHD-related structural correlates of amygdala functional activity elicited during a functional MRI task designed to test behavioural and brain responses to the imposition of delay - an event known to both elicit amygdala hyperactivation and aversity in ADHD., Methods: Structural MRI scans from 28 right-handed male adolescents with combined type ADHD and 32 age-matched controls were analysed. Regional grey matter volumes of ADHD and control participants ( P [FWE] < 0.05) were correlated with delay aversion self-ratings and neural activity in response to delay-related cues on the Escape Delay Incentive fMRI task., Results: ADHD was associated with significantly reduced volumes in bilateral amygdala, parahippocampal and temporal gyrus ( P [FWE] < 0.05), greater basolateral amygdala activation to delay-related cues ( P [FWE] < 0.05) and higher delay aversion self-ratings. Amygdala volume reductions were significantly correlated with, and statistically mediated the pathway from ADHD to, delay-cue-related amygdala hyperactivity ( P  < 0.01) and self-reported delay aversion ( P  < 0.01)., Conclusions: We provide the first evidence of the functional significance of reduced amygdala volumes in adolescents with ADHD by highlighting its relation to delay-induced brain activity that is linked to delay aversion.

Purpose: This study was performed to introduce an in vivo hybrid multimodality technique involving the coregistration of micro-computed tomography (micro-CT) and high-resolution magnetic resonance imaging (HR-MRI) to concomitantly visualize and quantify mineralization and vascularization at follow-up in a rat model., Materials and Methods: Three adult female rats were randomly assigned as test subjects, with 1 rat serving as a control subject. For 20 weeks, the test rats received a weekly intravenous injection of 30 µg/kg zoledronic acid, and the control rat was administered a similar dose of normal saline. Bilateral extraction of the lower first and second molars was performed after 10 weeks. All rats were scanned once every 4 weeks with both micro-CT and HR-MRI. Micro-CT and HR-MRI images were registered and fused in the same 3-dimensional region to quantify blood flow velocity and trabecular bone thickness at T0 (baseline), T4 (4 weeks), T8 (8 weeks), T12 (12 weeks), T16 (16 weeks), and T20 (20 weeks). Histological assessment was the gold standard with which the findings were compared., Results: The histomorphometric images at T20 aligned with the HR-MRI findings, with both test and control rats demonstrating reduced trabecular bone vasculature and blood vessel density. The micro-CT findings were also consistent with the histomorphometric changes, which revealed that the test rats had thicker trabecular bone and smaller marrow spaces than the control rat., Conclusion: The combination of micro-CT and HR-MRI may be considered a powerful non-invasive novel technique for the longitudinal quantification of localized mineralization and vascularization., Competing Interests: Conflicts of Interest: None, (Copyright © 2020 by Korean Academy of Oral and Maxillofacial Radiology.)

Background and Objective: While osseointegration following various dental implant placement protocols has been extensively investigated, the neurohistological integration has received little attention. The primary aim of this study was to compare the myelinated nerve fibers density in peri-implant bone tissue following various implant placement protocols. The secondary aim assessed the effect of follow-up on peri-implant nerve fibers density., Methods: Ten beagle dogs randomly received 68 commercially pure titanium implants in the mandibular premolar or molar region bilaterally following extraction utilizing one of the six treatment protocols: (a) immediate implant placement (IIP) and immediate loading (IL); (b) IIP and delayed loading (DL); (c) IIP and left unloaded (UL); (d) delayed implant placement (DIP) and IL; (e) DIP and DL; and (f) DIP and UL. Histomorphometric analysis of the peri-implant myelinated nerve fibers was performed in a 300 μm peri-implant zone at the cervical, middle, and apical level following implant placement. The follow-up assessment involved longitudinal observation at 3 months following each implant treatment protocol and at 6 months for IIP+IL and IIP+DL protocols., Results: The influence of different treatment protocols, including the fixed effects of implant groups (IIP+IL, IIP+DL, IIP+UL, DIP+IL, DIP+DL, DIP+UL) and regions (cervical, middle, apical), was examined via a linear mixed model. The IIP+IL group showed a significantly higher myelinated nerve density compared to the IIP+UL and DIP+UL group. Peri-implant nerve re-innervation was significantly higher (P = .002) in the apical region compared to the cervical region. After immediate implant placement, the IL group showed a significantly (P = .03) higher density of myelinated nerve fibers compared to DL. No significant (P = .19) effect of follow-up on nerve density was observed., Conclusion: The immediate implant placement and loading protocol showed most beneficial effect on peri-implant innervation with highest myelinated nerve density in the apical region. A longer loading time had no influence on the peri-implant nerve density., (© 2020 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.)

Objective: To investigate the relationship between preoperative trabecular bone structure and implant outcome based on bone morphometric bone parameters from CBCT scans., Materials and Methods: Twenty consecutive cases with early implant failure in the posterior region of the mandible were matched with 20 control patients with a successful implant osseointegration selected. All patients had taken a preoperative CBCT image according to a standardized acquisition protocol. On these CBCT scans, the trabecular bone of each implantation site was selected and segmented, after which 3D morphometric bone parameters were calculated and used in a cluster analysis to objectively differentiate trabecular bone patterns. Fisher's exact test was used to determine whether there is a significant association between trabecular pattern and implant outcome., Results: A sparse, intermediate, and dense trabecular bone pattern was distinguished by cluster analysis. The relationship between the trabecular bone pattern and early implant failure was significant (z = 9.6; p < .05). Early implant failure was more likely to occur in the sparse bone types, while implant survival was associated with intermediate bone types., Conclusion: Prior to implant placement, attention should be given to extreme deviations in trabecular structure at the planned implant sites. Very sparse or very dense bone should be carefully evaluated at the potential implant site, while intermediate bone types seem favorable for implant survival., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The aim of the study was to evaluate whether the use of a xenograft is not inferior to the use of xenograft and autogenous bone chips in treating dehiscences at implant placement., Materials and Methods: After implant placement, leaving a dehiscence, control sites were treated using a composite graft (autogenous bone chips and xenograft) and at the test sites 100% xenograft was used. Both sites were covered with a resorbable collagen membrane. Dehiscences were measured clinically at implant placement and at re-entry. CBCT was taken immediately after implant placement and after 4 months., Results: In total, 28 GBR procedures were performed in 14 patients. On average, the change in vertical defect height was 2.07 mm (46.7%-test group) and 2.28 mm (50.9%-control group) (p > .05). The horizontal defect width at the implant shoulder change on average 1.85 mm (40.5%-test group) and 1.75 mm (40.9%-control group) (p > .05). On average, a loss in augmentation thickness of 0.45 mm (68.9%-test group) and 0.64 mm (55.5% control group) between implant placement and augmentation and abutment surgery was obtained at the implant shoulder., Conclusion: Both treatment modalities seem to work to a certain extent. At implant shoulder level, the augmentation thickness seems to be disappeared after the healing phase. (NCT03946020)., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Autologous plasma fractions, such as platelet-rich plasma (PRP) and platelet-poor plasma (PPP), contain growth factors that can enhance neural cell survival and are therefore likely to have the ability to promote nerve regeneration. The present study compared the effect of PRP and PPP application on myelinated nerve density and diameter in the peri-implant bone region. In addition, the effect of healing time on nerve regeneration was assessed., Materials and Methods: Nine beagle dogs randomly received 54 dental implants in the bilateral mandible according to a split-mouth design. Each implant was randomly assigned to one of three implant protocols: delayed implant placement with delayed loading (DIP + DL) with local application of PRP, DIP + DL with local application of PPP and DIP + DL without any plasma additive. The animals were euthanized at 1, 3, and 6 months after loading (3 dogs per time point). Block biopsies were prepared for histomorphometry in the peri-implant bone within 500 μm around the implants., Results: Myelinated nerve fibers were identified in the trabecular bone and in the osteons near the implants surface. The nerve fibers in the PRP group (median ± IQR; 2.88 ± 1.55 μm) had a significantly (p < 0.05) greater diameter compared to the PPP (2.40 ± 0.91 μm) and control (2.11 ± 1.16 μm) group. The nerve diameter after 6 months healing (3.18 ± 1.58 μm) was significantly (p < 0.05) greater compared to 1 (2.08 ± 0.89 μm) and 3 (2.49 ± 1.22 μm) months. No significant difference was found for myelinated nerve density between groups and healing time., Conclusions: The present study showed that the healing time significantly influenced the diameter of the myelinated nerve fibers in peri-implant bone. PRP exerted a significant effect on the diameter of the myelinated nerve fibers as compared to PPP. Large-scale animal studies and longer follow-up periods are needed to confirm these findings and to verify whether platelet plasma can facilitate nerve regeneration process.